Skip to main content Accessibility help
×
Home
Hostname: page-component-564cf476b6-s5ssh Total loading time: 0.312 Render date: 2021-06-20T08:10:35.784Z Has data issue: true Feature Flags: { "shouldUseShareProductTool": true, "shouldUseHypothesis": true, "isUnsiloEnabled": true, "metricsAbstractViews": false, "figures": true, "newCiteModal": false, "newCitedByModal": true, "newEcommerce": true }

Defining CT Perfusion Thresholds for Infarction in the Golden Hour and With Ultra-Early Reperfusion

Published online by Cambridge University Press:  19 February 2018

Mohamed Najm
Affiliation:
Calgary Stroke Program, Department of Clinical Neurosciences, University of Calgary, Calgary, Alberta, Canada Seaman Family MR Research Centre, Foothills Medical Centre, Calgary, Alberta, Canada
Fahad S. Al-Ajlan
Affiliation:
Calgary Stroke Program, Department of Clinical Neurosciences, University of Calgary, Calgary, Alberta, Canada Department of Radiology, University of Calgary, Calgary, Alberta, Canada Department of Neurosciences, King Faisal Specialist Hospital & Research Centre, Riyadh, Saudi Arabia
Mari E. Boesen
Affiliation:
Seaman Family MR Research Centre, Foothills Medical Centre, Calgary, Alberta, Canada
Lisa Hur
Affiliation:
Calgary Stroke Program, Department of Clinical Neurosciences, University of Calgary, Calgary, Alberta, Canada
Chi Kyung Kim
Affiliation:
Calgary Stroke Program, Department of Clinical Neurosciences, University of Calgary, Calgary, Alberta, Canada Department of Neurology, Korea University Guro Hospital, Seoul, South Korea
Enrico Fainardi
Affiliation:
Neuroradiology Unit, Department of Diagnostic Imaging, Azienda Ospedaliero-Universitaria Careggi, Firenze, Italy
Michael D. Hill
Affiliation:
Calgary Stroke Program, Department of Clinical Neurosciences, University of Calgary, Calgary, Alberta, Canada Department of Radiology, University of Calgary, Calgary, Alberta, Canada Department of Community Health Sciences, University of Calgary, Calgary, Alberta, Canada Hotchkiss Brain Institute, Calgary, Canada Seaman Family MR Research Centre, Foothills Medical Centre, Calgary, Alberta, Canada
Andrew M. Demchuk
Affiliation:
Calgary Stroke Program, Department of Clinical Neurosciences, University of Calgary, Calgary, Alberta, Canada Department of Radiology, University of Calgary, Calgary, Alberta, Canada Hotchkiss Brain Institute, Calgary, Canada Seaman Family MR Research Centre, Foothills Medical Centre, Calgary, Alberta, Canada
Mayank Goyal
Affiliation:
Calgary Stroke Program, Department of Clinical Neurosciences, University of Calgary, Calgary, Alberta, Canada Department of Radiology, University of Calgary, Calgary, Alberta, Canada Hotchkiss Brain Institute, Calgary, Canada Seaman Family MR Research Centre, Foothills Medical Centre, Calgary, Alberta, Canada
Ting Y. Lee
Affiliation:
Department of Radiology, University of Calgary, Calgary, Alberta, Canada Lawson Health Research Institute and Robarts Research Institute, London, Ontario, Canada
Bijoy K. Menon
Affiliation:
Calgary Stroke Program, Department of Clinical Neurosciences, University of Calgary, Calgary, Alberta, Canada Department of Radiology, University of Calgary, Calgary, Alberta, Canada Department of Community Health Sciences, University of Calgary, Calgary, Alberta, Canada Hotchkiss Brain Institute, Calgary, Canada Seaman Family MR Research Centre, Foothills Medical Centre, Calgary, Alberta, Canada
Corresponding
E-mail address:
Rights & Permissions[Opens in a new window]

Abstract

In this brief report, computed tomography perfusion (CTP) thresholds predicting follow-up infarction in patients presenting <3 hours from stroke onset and achieving ultra-early reperfusion (<45 minutes from CTP) are reported. CTP thresholds that predict follow-up infarction vary based on time to reperfusion: Tmax >20 to 23 seconds and cerebral blood flow <5 to 7 ml/min−1/(100 g)−1 or relative cerebral blood flow <0.14 to 0.20 optimally predicted the final infarct. These thresholds are stricter than published thresholds.

Résumé

Seuils limites d’un examen de tomodensitométrie couplé à une perfusion administré à des patients victimes d’un accident ischémique et aux prises avec un processus de reperfusion très précoce se présentant en temps opportun. Dans ce bref compte-rendu, il est question des seuils limites obtenus à la suite d’un examen de tomodensitométrie couplé à une perfusion. Ces seuils limites peuvent prédire le suivi de patients ayant subi un accident ischémique. Les patients à l’étude devaient s’être présentés moins de 3 heures après l’apparition de l’accident ischémique et avoir montré très tôt des signes de reperfusion (moins de 45 minutes à la suite d’un examen de tomodensitométrie). Les seuils limites pouvant prédire l’évolution de patients à la suite d’un accident ischémique vont varier selon le temps de reperfusion. Cela dit, une durée dépassant les 20 à 23 secondes et un débit sanguin cérébral inférieur à 5-7 ml/min−1/(100 g)−1 ou bien un débit sanguin cérébral relatif inférieur à 0,14-0,20 ont permis de prédire de façon optimale un AVC. Précisons que ces seuils limites sont plus sévères que ceux ayant été publiés antérieurement.

Type
Brief Communications
Copyright
Copyright © The Canadian Journal of Neurological Sciences Inc. 2018 

At the exact time a thrombus blocks an intracranial artery, downstream blood flow drops. Depending on collateral extent, ischemic brain can have regions of flow ranging from very low to near normal. Regions with very low blood flow are likely to infarct earlier; nonetheless, these brain regions will remain viable for a short period. Computed tomography perfusion (CTP) thresholds predicting infarction on follow-up brain scans are therefore likely to depend on how fast reperfusion is achieved, and could break down if reperfusion is achieved ultra-early.

With modern endovascular therapy and a strong focus on efficiency in workflow, ultra-early reperfusion is now achievable.Reference Goyal, Demchuk and Menon 1 Using data from a large prospective cohort study, we reported time-based CTP thresholds predicting follow-up infarction among patients achieving imaging to reperfusion in <90 minutes and <180 minutes, on average.Reference d’Esterre, Boesen and Ahn 2 In this analysis, using data from a subset of patients achieving ultra-early CTP-to-reperfusion time (<45 minutes) and early onset to admission imaging (<3 hours), we estimate CTP thresholds predicting follow-up brain infarction.

We queried the Prove-IT database for patients satisfying the following inclusion criteria: (1) >18 years of age; (2) complete anterior circulation proximal vessel occlusion; (3) TICI 2b/3 reperfusion within 45 minutes of admission CTP; (4) onset to admission imaging within 180 minutes; and (5) 24-hour follow-up magnetic resonance-diffusion-weighted imaging preferably or noncontrast computed tomography (NCCT) if magnetic resonance imaging is not available. Demographic and clinical characteristics, imaging, and interval times were collected.

A 64-slice CT scanner (Lightspeed; GE Healthcare, Waukesha, WI) was used for all CT imaging. NCCT, head/neck multiphase CT angiography, and CTP were performed at admission. NCCT and multislice CTA were done per described protocol.Reference Menon, d’Esterre and Qazi 3 For the CTP protocol, 45 ml CT contrast agent (Optiray 320; Mallinckrodt Pharmaceuticals, Dublin, Ireland) was power injected at 4.5 ml/s followed by a saline chase of 40 ml at 6 ml/s. An 8-cm slab of the brain in 5-mm-thick slices was scanned using two phases: a 2.8-second interval for 60 seconds, then a 15-second interval for 90 seconds.

Delay-insensitive deconvolution software (CT Perfusion 4D, GE Healthcare) was used for CTP processing. The arterial input function was manually selected from the basilar artery or internal carotid artery. Cerebral blood flow (CBF) [ml/min−1/(100 g)−1], cerebral blood volume (CBV) [ml/(100 g)−1], and Tmax (seconds) maps were calculated.Reference d’Esterre, Boesen and Ahn 2 Average maps were used for gray/white matter segmentation and as the source image for coregistration with follow-up imaging.Reference d’Esterre, Boesen and Ahn 2 CTP maps and follow-up images were coregistered using in-house software (Calgary Image Analysis and Processing Centre, Calgary, AB).

An expert radiologist (CK) delineated the follow-up infarct, when present, on diffusion-weighted imaging (n=5) or NCCT (n=2) superimposed onto coregistered CTP functional maps. Method for optimal threshold derivation has been described previously.Reference d’Esterre, Boesen and Ahn 2 Briefly, voxel-level histograms were extracted from the infarct (region of interest-infarct) and the ipsilateral hemisphere minus the infarct (region of interest-salvaged). Receiver operating characteristic curve was generated from the histograms. Youden’s method was then used to determine optimal threshold associated with follow-up infarction for each CTP parameter. Corresponding relative CBF thresholds were also calculated.

Seven patients satisfied inclusion criteria. Among these, three had onset to CTP ≤60 minutes (golden hour), whereas four had onset to CTP 60 to 180 minutes. Median (range) onset to CTP time was 148 minutes (52-180 minutes), CTP to final reperfusion time was 41 minutes (29-45 minutes), admission National Institutes of Health Stroke Scale was 11 (6-17) (Table 1). Optimal CTP thresholds, stratified by onset-to-CTP time, along with c-statistics and sensitivities/specificities, are shown in Table 2. Tmax >22 to 23 seconds and CBF <5.5 ml/min−1/(100 g)−1 or relative CBF <0.16 were optimal when reperfusion was achieved in patients resenting in the golden hour and achieving reperfusion within 45 minutes of baseline CTP. CTP thresholds for patients presenting within 3 hours of symptom onset but beyond the golden hour still achieving ultra-early reperfusion are slightly more liberal (Table 2).

Table 1 Admission demographics and workflow time metrics in the study (n=7)

CTP=computed tomography perfusion; mTICI=modified treatment in cerebral ischemia; NIHSS=National Institutes of Health Stroke Scale

Table 2 Optimal CTP thresholds from voxel level data in patients achieving ultra-early reperfusion (CTP to reperfusion <45 minutes), stratified by imaging within “golden hour” (onset to CTP ≤60 minutes) versus early (onset to CTP 60-180 minutes)

* Significantly different from other parameters in that strata.

AUC=area under the receiver operator characteristic curve (c-statistic); CBF=cerebral blood flow; CI=confidence interval; CTP=computed tomography perfusion

With better in-field triaging, efficient in-hospital workflow, and modern endovascular therapy, reperfusion times continue to get faster. Recently, we showed that a Tmax threshold of >16 seconds or absolute CBF threshold of <9 ml/min−1/(100 g)−1 (relative CBF <0.23) is associated with infarct if quality reperfusion is achieved within 90 minutes from CTP imaging.Reference d’Esterre, Boesen and Ahn 2 Herein, we show that CTP thresholds predicting follow-up infarction continue to evolve based on time to quality reperfusion. On average, Tmax >20 to 23 seconds and CBF <5 to 7 ml/min−1/(100 g)−1 or relative CBF <0.14 to 0.20 were optimal when reperfusion was achieved within 45 minutes of baseline CTP. These thresholds are lower than those for reperfusion within 90 minutesReference d’Esterre, Boesen and Ahn 2 and more stringent in the golden hour (Figure 1). Moreover, relative CBF thresholds from this analysis are much lower than current accepted thresholds.Reference Bivard, Levi and Krishnamurthy 4 - Reference Campbell, Christensen and Levi 6

Figure 1 Updated hypothetical model for ischemic core prediction.Reference d’Esterre, Boesen and Ahn 2 In addition to previously published thresholds,Reference d’Esterre, Boesen and Ahn 2 thresholds for “golden hour” patients (Tmax >23 seconds) and for patients imaged between 60 and180 minutes after stroke onset (Tmax >20 seconds) who achieve reperfusion within 45 minutes of CTP are shown along with the corresponding relative CBF threshold.

Although recent studies, including ours, empirically report that CTP thresholds predictive of follow-up infarction do not vary substantively by onset to CT time,Reference d’Esterre, Boesen and Ahn 2 , Reference Qiao, Zhu and Patrie 7 but depend on imaging to reperfusion time, our results show that Tmax and CBF thresholds predicting follow-up infarction become stricter (higher for Tmax, lower for CBF) with early onset to imaging times. In our opinion, this could be because measurement onset time is more accurate the earlier a patient presents to hospital. We also note that the sensitivity and specificity of these thresholds in predicting infarct are slightly lower in the golden hour. Plausible explanation is that CTP measures blood flow rather than neuronal function and very early in the ischemic cascade the survival threshold is more heterogeneous if reperfusion can be established quickly. Interestingly, in the golden hour, the CBV parameter becomes as discriminative (c-statistic for gray matter and white matter of 0.81 and 0.80, respectively), if not more than the other parameters. If CBV is low (<2.6-2.7 ml/(100 g)−1), then that tissue has a very high likelihood of irreversible infarction, even if reperfusion occurs in <45 minutes. Conversely, if CBV is >2.7 ml/(100 g)−1and reperfusion occurs in <45 minutes, then that tissue has a high likelihood of surviving. The effect that ultra-early presentation and reperfusion has on the predictive characteristics of CTP thresholds are illustrated in the Supplemental Figure.

Ultra-early presentation and reperfusion is uncommon; we only identify seven such patients from a study of more than 500 patients. Nonetheless, the voxel-level analysis we performed gives our analysis some robustness. In summary, we show that with faster reperfusion time, CTP thresholds become more stringent. These stricter CTP thresholds may need to be considered when patients present very early to a community hospital and need to be triaged to an endovascular capable hospital. If the predicted infarct size using these thresholds is moderate to large, an argument could be made for futility of transfer. A larger sample will be needed however to better understand the biological underpinnings behind our work and to increase generalizability of these CTP thresholds.

ACKNOWLEDGEMENTS AND FUNDING

The authors thank the Calgary Stroke Program Team, Calgary, Alberta, Canada, and University Hospital.

This study is funded through an operating grant (PRoveIT) from the Canadian Institute of Health Research.

Disclosures

BKM, MDH, MG, AMD, and TYL have a patent pending on systems of triage in acute stroke. MDH, MG, AMD, TYL, and BKM hold stock in QuikFlo Health Inc. MG has a patent on systems of stroke diagnosis using multiphase computed tomographic angiography and a licensing agreement with GE Healthcare for the same. MDH and MG have a research grant with Covidien to conduct clinical trials. TYL licenses CT Perfusion software to GE Healthcare. The remaining authors have nothing to declare.

SUPPLEMENTARY MATERIAL

To view supplementary material for this article, please visit https://doi.org/10.1017/cjn.2017.287

Footnotes

Part of these results was presented the 68th AAN Annual Meeting, April 15-21, 2016, Vancouver, BC, Canada.

References

1. Goyal, M, Demchuk, AM, Menon, BK, et al. ESCAPE Trial Investigators. Randomized assessment of rapid endovascular treatment of ischemic stroke. N Engl J Med. 2015;372:1019-1030.CrossRefGoogle ScholarPubMed
2. d’Esterre, CD, Boesen, ME, Ahn, SH, et al. Time-dependent computed tomographic perfusion thresholds for patients with acute ischemic stroke. Stroke. 2015;46:3390-3397.CrossRefGoogle ScholarPubMed
3. Menon, BK, d’Esterre, CD, Qazi, EM, et al. Multiphase CT angiography: a new tool for the imaging triage of patients with acute ischemic stroke. Radiology. 2015:142256.Google ScholarPubMed
4. Bivard, A, Levi, C, Krishnamurthy, V, et al. Defining acute ischemic stroke tissue pathophysiology with whole brain ct perfusion. J Neuroradiol. 2014;41:307-315.CrossRefGoogle ScholarPubMed
5. Bivard, A, Levi, C, Spratt, N, Parsons, M. Perfusion ct in acute stroke: a comprehensive analysis of infarct and penumbra. Radiology. 2013;267:543-550.CrossRefGoogle ScholarPubMed
6. Campbell, BC, Christensen, S, Levi, CR, et al. Cerebral blood flow is the optimal ct perfusion parameter for assessing infarct core. Stroke. 2011;42:3435-3440.CrossRefGoogle ScholarPubMed
7. Qiao, Y, Zhu, G, Patrie, J, et al. Optimal perfusion computed tomographic thresholds for ischemic core and penumbra are not time dependent in the clinically relevant time window. Stroke. 2014;45:1355-1362.CrossRefGoogle Scholar
Supplementary material: File

Najm et al. supplementary material

Supplemental Figure

Download Najm et al. supplementary material(File)
File 810 KB
You have Access
10
Cited by

Send article to Kindle

To send this article to your Kindle, first ensure no-reply@cambridge.org is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about sending to your Kindle. Find out more about sending to your Kindle.

Note you can select to send to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be sent to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

Find out more about the Kindle Personal Document Service.

Defining CT Perfusion Thresholds for Infarction in the Golden Hour and With Ultra-Early Reperfusion
Available formats
×

Send article to Dropbox

To send this article to your Dropbox account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Dropbox.

Defining CT Perfusion Thresholds for Infarction in the Golden Hour and With Ultra-Early Reperfusion
Available formats
×

Send article to Google Drive

To send this article to your Google Drive account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Google Drive.

Defining CT Perfusion Thresholds for Infarction in the Golden Hour and With Ultra-Early Reperfusion
Available formats
×
×

Reply to: Submit a response

Please enter your response.

Your details

Please enter a valid email address.

Conflicting interests

Do you have any conflicting interests? *